Exploring the Role of Globular Domain Locations on an Intrinsically Disordered Region of p53: A Molecular Dynamics Investigation
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F24%3A10493140" target="_blank" >RIV/00216208:11160/24:10493140 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=QnV7VQEgL3" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=QnV7VQEgL3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jctc.3c00971" target="_blank" >10.1021/acs.jctc.3c00971</a>
Alternative languages
Result language
angličtina
Original language name
Exploring the Role of Globular Domain Locations on an Intrinsically Disordered Region of p53: A Molecular Dynamics Investigation
Original language description
The pre-tetramerization loop (PTL) of the human tumor suppressor protein p53 is an intrinsically disordered region (IDR) necessary for the tetramerization process, and its flexibility contributes to the essential conformational changes needed. Although the IDR can be accurately simulated in the traditional manner of molecular dynamics (MD) with the end-to-end distance (EEdist) unhindered, we sought to explore the effects of restraining the EEdist to the values predicted by electron microscopy (EM) and other distances. Simulating the PTL trajectory with a restrained EEdist , we found an increased agreement of nuclear magnetic resonance (NMR) chemical shifts with experiments. Additionally, we observed a plethora of secondary structures and contacts that only appear when the trajectory is restrained. Our findings expand the understanding of the tetramerization of p53 and provide insight into how mutations could make the protein impotent. In particular, our findings demonstrate the importance of restraining the EEdist in studying IDRs and how their conformations change under different conditions. Our results provide a better understanding of the PTL and the conformational dynamics of IDRs in general, which are useful for further studies regarding mutations and their effects on the activity of p53.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GJ19-14886Y" target="_blank" >GJ19-14886Y: Reliable calculations and predictions of NMR chemical shifts for the structural characterization of phosphorylated intrinsically disordered proteins</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Chemical Theory and Computation
ISSN
1549-9618
e-ISSN
1549-9626
Volume of the periodical
20
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
1423-1433
UT code for WoS article
001162263100001
EID of the result in the Scopus database
2-s2.0-85183495090